Fungi are the typical eukaryotes having the nuclei and organelles. When fungi invade in the skin tissue, it causes Dermatomycoses. When fungi invade in the human body via the lung, that is, when they infect our body, they cause various diseases such as systemic mycoses and opportunistic mycoses particularly in those people whose immunity has been weakened, for example those with AIDS or with organ transplantation, etc.
Even though the necessity of antifungal agents for the treatment of the said diseases has been well understood, the medicine on the market to treat systemic infection is rare. Recently an antifungal agent targeting a specific component of cell wall, for example echinocandins, has been developed. However, most drugs including amphotericin B, azole containing nystatin, and polyene, are targeting the whole structure of fungal membrane.
The azole antifungal drugs have been widely used because they have less side effects. However, according to the recent increase of azole resistant fungi and the increased incidence rate of the infection by such resistant fungi, the treatment of the disease is in trouble, requiring the development of a new antifungal agent.
Polyenes are very interesting polykotone macrolide drugs that demonstrate active antifungal activity. These compounds include macrolactone rings having multiple conjugated double bonds that form a chromophore showing a characteristic spectrum in ultraviolet/visible ray region.
The antifungal activity of such antifungal agents as nystatin and amphotericin B is induced by the interaction between polyene molecules and the membrane comprising sterol. This interaction forms an ion channel and the membrane is now permeable therefore to destroy electrochemical gradient, leading to the death of the fungal cell. The said compounds have a great affinity rather to those membranes containing ergosterol (the major sterol found on the membranes of fungi and parasites such as Trypanosoma and Leishmania) than to those membranes containing cholesterol (mammalian cells). However, the interaction between polyene molecules and the membrane containing cholesterol is not meaningless, either. Owing to the side effects such as hemolytic activity along with low-solubility, these compounds do not satisfy the treatment of systemic fungal infection as a whole. Particularly, there is no better alternative than the polyene compounds to fight with fungal infection.
To overcome the problems of the conventional antifungal agents, the present inventors judged that the polyene compounds such as amphotericin B and nystatin would be clinically more practical than the azole compounds. Therefore, the present inventors tried to find out a novel polyene antifungal compound. As a result, the present inventor completed this invention by identifying a novel polyene compound having antifungal activity which also displayed improved solubility and less hemolytic activity while retaining antifungal activity.